In this research project, the changes occurring in the hepatic metabolism of insulin in response to fasting will be studied in control fed rats at various time points after initiation of a two hour meal. Fasting-induced alterations in insulin metabolism will be assessed by correlating hepatic glutathione-insulin transhydrogenase activity and % latency, measured enzymatically, with endogenous insulin clearance capacity recorded in perfused liver-pancreas preparations. In addition, the influence of hormonal and other factors capable of modulating insulin binding and/or degradation on the ability of the perfused liver to clear insulin in these preparations will also be assessed. These studies in conjunction with the enzyme and clearance data collected during the early fasting period should significantly add to our understanding of the dynamic aspects of the liver's role in the regulation of insulin blood level in the normal animal. The effects of prolonged fasting on insulin clearance and degradation in perfused liver-pancreas preparations will provide additional information about autoregulation of insulin blood level and the associated changes in hepatic insulin metabolism occurring in insulin deficient states.